Neocortical and thalami neurons and neuronal circuits display different patterns of activity in vivo which range from rhythmic oscillations during slow wave sleep to relatively de-synchronous activity during waking and attentiveness. These different patterns of activity greatly affect the ability of corticothalamic circuits to generate both normal (e.g. cognition, arousal, learning and memory) and abnormal (e.g. absence seizures) activity. The overall pattern of activity and neuronal excitability in cortical and thalamic systems are regulated by modulatory transmitter systems arising from the brainstem, basal forebrain, hypothalamus, and cerebral cortex and involve the release of acetylcholine, norepinephrine, serotonin, histamine, and glutamate. The long term goal of our laboratory is to understand the ionic and subcellular mechanisms by which thalamocortical circuits generate different patterns of activity, how neuromodulatory transmitter actions may determine these different patterns of activity, and the functional consequences of these changes in activity. Towards achieving this long term goal, we are investigating the ionic mechanisms of action of all of the above mentioned neurotransmitters on identified neurons in the thalamic and cortical visual system using intracellular recording techniques performed on slices of brain tissue maintained in vitro. By investigating the basic electrophysiological and pharmacological properties of identified neurons in the visual cortex and visual thalamus, we hope to form a "circuit diagram: which illustrates the basic mechanisms of ascending and descending modulation of thalamocortical activity during the sleep/wake cycle and during periods of arousal and attentiveness. The goal of the present proposal are: 1) to detail the physiological properties of the descending projection form the visual cortex to the dorsal lateral geniculate nucleus, particularly the ability of this pathway to activate glutamate metabotropic receptors; 2) to detail the actions of modulatory transmitters on neurons in the extrageniculate visual thalamus; and 3) to detail the physiology and pharmacological responses of identified subtypes of neurons in the primary visual cortex (area 17). By understanding the cellular mechanisms of thalamocortical processing, we will greatly increase our understanding of a number of normal and abnormal cognitive processes.